Rapidly dividing cells require cobalamin as a cofactor for the enzyme methionine synthase to support one-carbon metabolism prior to DNA replication. In acute promyelocytic leukemia, a 3-26 fold increase in the unsaturated B12 binding capacity of blood is observed, due to an increase in the concentration of the B12 binding proteins transcobalamin and haptocorrin. Some patients with solid tumors also exhibit a significant increase in the circulating levels of transcobalamin and haptocorrin. The increase in unsaturated serum cobalamin binding capacity corresponds to the increased uptake of cobalamin by rapidly dividing cells. Tumors sequester sufficient cobalamin for diagnostic imaging purposes if a gamma-emitting radionuclide, such as 111In, is attached to cobalamin through the octadentate chelator diethylenetriaminepentaacetic acid (DTPA). This has been demonstrated in mice with an implanted fibrosarcoma, as well as in humans with breast cancer, and in tumors of the prostate, lung and brain.
In the sentinel lymph node concept for melanoma and breast cancer surgery, a dye or radionuclide is injected into the tissue around the tumor to identify the first lymph node that drains the tumor and its surrounding tissue. This node is termed the sentinel node, and it is removed for diagnostic tests to determine the extent of metastasis beyond the primary tumor. This procedure is controversial, as it fails to detect metastatic disease in about 12% of patients. The dye or radionuclide that is injected is not specific for cancer cells, but merely identifies for the surgeon the primary lymph node that drains the region of the tumor. The high false-negative rate should be improved dramatically by using a fluorescent marker that is specific for cancer cells. More than one, but typically less than four, lymph nodes may be identified by this procedure as the “sentinel” lymph node.
Thus, there exists a need for agents and instruments that can be used for the diagnosis, prognosis, and removal of cancer tissue or cells to improve patient disease outcomes.